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Blood, 1 July 2008, Vol. 112, No. 1, pp. 120-130.
Prepublished online as a Blood First Edition Paper on March 6, 2008; DOI 10.1182/blood-2007-09-114181.


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Submitted September 24, 2007
Accepted March 4, 2008

Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes

Scot D. Liu, Chan C Whiting, Tamar Tomassian, Mabel Pang, Stephanie J Bissel, Linda G Baum, Valeri V. Mossine, Francoise Poirier, and M. Carrie Miceli*

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States
Ingenuity Systems, Partner & Professional Services, Redwood City, CA, United States
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, United States
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, United States
Department of Biochemistry, University of Missouri, Columbia, MO, United States
Institut Jacques Monod, Centre National de la Recherche Scientifique Unite Mixte de Recherche, Paris, France

* Corresponding author; email: cmiceli{at}ucla.edu.

During thymocyte development, the TCR can discriminate MHC/peptide ligands over a narrow range of affinities and translate subtle differences into functional fate decisions. How small differences in TCR input are translated into absolute differences in functional output is unclear. We examined the effects of galectin-1 ablation in the context of class-I-restricted thymocyte development. Galectin-1 expression opposed TCR partial agonist-driven positive selection, but promoted TCR agonist-driven negative selection of conventional CD8+ T cells. Galectin-1 expression also promoted TCR agonist-driven CD8{alpha}{alpha} IEL development. Recombinant galectin-1 enhanced TCR binding to agonist/MHC complexes and promoted a negative-selection-signaling signature, reflected in intensified rapid and transient ERK activation. In contrast, galectin-1 expression antagonized ERK activity in thymocytes undergoing positive selection. We propose that galectin-1 aids in discriminating TCR-directed fate decisions by promoting TCR binding to agonist/MHC complexes and enforcing agonist-driven signals, while opposing partial-agonist signals. In this way, galectin-1 widens the distinction between TCR-directed functional fate cues.


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